Mechanisms of Mycobacterial-Induced Immunity in HIV-Infected and/or Uninfected Individuals to Inform Innovative Tuberculosis Vaccine Design (R01 Clinical Trial Not Allowed) | PAR 19 307

FAQs: NIH PAR-19-307 (R01) - Mechanisms of Protective Immunity to Mycobacterium tuberculosis

What is NIH PAR-19-307?

PAR-19-307 is an NIH funding opportunity announcement (FOA) using the R01 research project grant mechanism. It supports research aimed at identifying and explaining the immune responses that actually protect people from Mycobacterium tuberculosis (Mtb) infection or from progressing to active tuberculosis (TB) disease after exposure or infection.

What is the main scientific goal of this FOA?

The main goal is to generate mechanistic evidence of protective immunity to Mtb. Projects are expected to go beyond listing biomarkers or reporting correlations and instead clarify how specific immune responses work, where and when they occur, and how they influence real outcomes such as resisting infection, controlling bacterial growth, maintaining latency, or progressing to symptomatic TB.

Why does this FOA emphasize "mechanism" rather than immune markers or associations?

The FOA is designed to fund work that distinguishes correlates from causes. The expectation is that applicants will explain why particular immune signatures appear and demonstrate how those responses contribute to protection versus progression, with results that can be used to inform vaccine design and improvement.

How does this funding opportunity connect to TB vaccine development?

The FOA is explicitly aimed at producing knowledge that can be used to design or improve next-generation TB vaccines. Mechanistic findings are intended to be actionable for decisions such as antigen selection, adjuvant or platform choices, route of immunization (including mucosal targeting), and strategies tailored to populations at highest risk, including people living with HIV.

What types of immune responses are of interest under PAR-19-307?

Protective immune responses to Mtb are the focus, including both mucosal immunity (for example, immune activity in the respiratory tract where Mtb first establishes infection) and systemic immunity (blood and broader immune compartments). The FOA highlights the importance of understanding how these responses develop over time and how they affect outcomes.

Does the FOA require research on mucosal immunity, systemic immunity, or both?

The FOA signals specific interest in mucosal and systemic responses and emphasizes integrating anatomical location, timing, and functional contribution. It also cautions against relying only on peripheral blood measurements when the key biology is rooted in the lungs or airways, while still allowing systemic analyses when appropriate to the question.

At what stage of TB infection can studies be conducted?

Studies can address any stage of infection or disease as long as the research is aimed at identifying immunological mechanisms that determine protection versus progression. The description includes early exposure, latent infection, incipient disease, and active TB as relevant contexts.

Can projects focus on immunity from natural infection, vaccination, or both?

Yes. Proposed studies may focus on immune responses that arise during natural mycobacterial infection, after vaccination with Bacillus Calmette-Guerin (BCG), or following receipt of investigational TB vaccines.

Are studies involving people living with HIV allowed?

Yes. The FOA allows studies that include HIV-infected individuals, HIV-uninfected individuals, or both. This reflects the major role HIV plays in TB susceptibility and the need for TB vaccines that perform well in settings where HIV is prevalent.

How are HIV and non-tuberculous mycobacterial (NTM) exposure treated in this FOA?

HIV and NTM exposure are framed as important variables that can shape immunity and vaccine performance. However, the FOA discourages surface-level profiling and expects deeper mechanistic insight into how these factors alter immune responses and influence protection versus progression.

What kinds of projects are not responsive to this FOA?

The FOA explicitly indicates it does not want purely descriptive work that remains within generally known information about Mtb infection, immune responses to TB vaccines, or immune modulation caused by NTM exposure and HIV/AIDS. Projects limited to cataloging immune markers or reporting associations without mechanistic explanation are not aligned with the stated expectations.

Does "Clinical Trial Not Allowed" mean human studies are prohibited?

No. The FOA title specifies "Clinical Trial Not Allowed" in the NIH sense, meaning applicants should not propose a clinical trial as defined by NIH rules. Studies may still involve human participants and clinical specimens, as long as the work is structured as mechanistic research rather than an interventional trial testing clinical outcomes.

What funding mechanism is used?

This is an NIH R01 research project grant opportunity.

What is the funding activity category?

The funding activity category listed is health.

What is the CFDA number associated with this opportunity?

The CFDA number listed for this opportunity is 93.855.

When was this opportunity created, and what closing date is shown?

The opportunity was created on June 28, 2019. The original closing date shown is September 10, 2020, which is important for historical context and for checking whether the FOA is still active or has been reissued in an updated form.

Who is eligible to apply?

Eligibility is broad and includes state, county, and local governments; public and private institutions of higher education; independent school districts; special district governments; federally recognized Native American tribal governments and other tribal organizations; public housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and other eligible entities.

Are minority-serving institutions specifically encouraged or eligible?

Yes. The FOA explicitly calls out additional eligible applicants including Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American and Native American Pacific Islander-Serving Institutions (AANAPISIs).

Are faith-based and community-based organizations eligible?

Yes. Faith-based or community-based organizations are explicitly listed among eligible applicants.

Can foreign (non-U.S.) organizations apply?

Yes. The FOA includes non-U.S. entities (foreign organizations) and regional organizations among eligible applicants, consistent with the global burden of TB and HIV and the value of accessing diverse cohorts and clinical settings.

Can eligible federal agencies apply?

Yes. Eligible federal agencies are specifically mentioned as additional eligible applicants.

Are U.S. territories or possessions eligible to apply?

Yes. U.S. territories or possessions are included in the list of additional eligible applicants.

What does NIH appear to want as the practical "deliverable" from funded projects?

The FOA is pushing for vaccine-relevant, actionable insight: a clearer map of immune mechanisms that can guide next-generation TB vaccine design and improvement, including approaches intended to work well in people living with HIV and in contexts shaped by environmental mycobacteria.

What makes a project competitive under PAR-19-307 based on the description provided?

Competitive projects would be expected to be hypothesis-driven and to integrate timing, anatomical location, and functional contribution of immune responses to real outcomes. They should propose strategies that help separate correlation from causation and explain how protective responses can be harnessed or induced by vaccination for durable protection.